Gold(I) catalysed cycloisomerisation of β-hydroxy propargylic esters to dihydropyrans/2H-pyrans via allene intermediates

Article abstract of DOI:10.1016/j.tet.2013.07.003

Efficient cycloisomerisation of β-hydroxy propargylic esters to dihydropyrans/2H-pyrans via 1,3-carboxylate migration followed by regioselective hydroxyl addition to the transient allene intermediate catalysed by Ph ₃PAuCl/AgSbF₆ is presented. Similar reactions on phosphorylated precursors led to phosphono-furans and phosphono-pyrans. In a few cases, self-condensation of β-hydroxy propargylic esters via catalytic nucleophilic substitution to macrocycles is observed. Key products are characterised by X-ray structure determination.

Full text of DOI:10.1016/j.tet.2013.07.003

Tetrahedron 69 (2013) 8002e8012
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Tetrahedron
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Gold(I) catalysed cycloisomerisation of
b-hydroxy propargylic esters
to dihydropyrans/2H-pyrans via allene intermediates
*
Ramesh Kotikalapudi, K.C. Kumara Swamy
School of Chemistry, University of Hyderabad, Hyderabad 500 046, A.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2013
Received in revised form 17 June 2013
Accepted 1 July 2013
Available online 5 July 2013
Efficient cycloisomerisation of
carboxylate migration followed by regioselective hydroxyl addition to the transient allene in-
termediate catalysed by Ph3PAuCl/AgSbF6 is presented. Similar reactions on phosphorylated precursors
led to phosphono-furans and phosphono-pyrans. In a few cases, self-condensation of b-hydroxy prop-
argylic esters via catalytic nucleophilic substitution to macrocycles is observed. Key products are char-
acterised by X-ray structure determination.
b-hydroxy propargylic esters to dihydropyrans/2H-pyrans via 1,3-
Keywords:
Gold catalysis
Ó 2013 Elsevier Ltd. All rights reserved.
Hydroxy propargylic ester
6-endo-trig Cyclisation
Pyran
Allene intermediate
1. Introduction
have recently reported the cycloisomerisation of u-hydroxy prop-
argylic esters to lead to tetrahydropyrans via 1,3-acyloxy migra-
Thanks to the recent flurry of activity, gold catalysis has now
been proven to be an effective method for the construction of CeC
and CeX bonds.1 Mild conditions like low catalyst loading, short
reaction time, ambient temperature conversions for regio- and
stereo-selective transformations involving highly functionalized
molecules have rendered gold catalysis an active area of research.2
As a consequence of alkynophilicity of gold salts, alkynols as well
as propargylic esters can be made to undergo rearrangement to
provide a variety of reactivity patterns.2a,3 Only a handful of reports
on the use of 2-alkynyl allyl alcohols to synthesise functionalised
carbocycles/furans via gold4 or silver5 catalysis are available. Our
recent discovery4e in using 2-alkynyl cinnamyl alcohols for the
synthesis of furans prompted us to examine a feasible six-mem-
bered (pyran) ring formation instead of furans. Dihydropyran ring
system is fairly common in biologically active natural products like
laulimalide,6aec ambruticin S,6d Scytophycin C,6e swinhol,6f,g methyl
sarcophytoate,6h which have anticancer, antifungal and antibiotic
activity.7 They are also valuable synthetic scaffolds for the genera-
tion of natural products,8 carbohydrates and functionalized pyri-
dines.9 2H-Pyran is also an important skeleton in biological
molecules like pyranoflavanoids.10 De Brabander and co-workers
tion.11 Considering the behaviour of propargylic ester group in the
presence of gold complexes, we synthesised b-hydroxy propargylic
esters I (Scheme 1) with a view to generate six-membered oxacycles
(pyrans). The reaction is supposed to proceed through allenic in-
termediate II, which on hydroxyl addition to the allene could lead to
pyran derivatives III.
R
OH
ref 4
R
O
(a)
R1
R1 = aryl. alkyl
R1
R
OH
R
O
R
ZO
OH
R2
R1
(b)
This
work
ZO
R1
R2
R1
R2
R1 = aryl. alkyl
R2 = H, alkyl
Z = Bz, Ac, EtC(O)
III
OZ
I
II (transient allenic intermediate)
* Corresponding author. Tel.: þ91 40 2313 4856; fax: þ91 40 2301 2460; e-mail
addresses: kckssc@uohyd.ernet.in, kckssc@uohyd.ac.in, kckssc@yahoo.com (K.C.
Kumara Swamy).
Scheme 1. Cycloisomerisation of 2-alkynyl allyl alcohols: (a) reported, (b) proposed.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.003

R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
8003
Although activation of allenes by AuI/AuIII is described earlier,
CHO
many of these result in five-membered ring formation12 and only in
a few cases, 6-endo-trig cyclisation is observed.13 Very recently,
work on racemic phenolic propargylic esters using gold(I)echiral
acyclic diaminocarbene complex for excellent chirality transfer is
reported by Toste’s group.14 We were also interested to apply Au(I)
catalysis using simpler ligands. Thus, as a useful and convenient
variation, herein we report gold(I) catalysed efficient cyclo-
Ph
3 mol % PdCl2
6 mol % PPh3
Ph
OH
CH3Li
-78 oC, THF
OBz
2
+
R
R
6 mol % CuI
iPr2NH, rt
R
OBz
OBz
24, 46%
R
3b-d
R = Me
21, 85%
(R,R) = [-CH2-]5 22, 82%
(R,R) = [-CH2-]4 23, 91%
isomerisation of our multifunctional b-hydroxy propargylic esters
4e20 and 24 [obtained easily using iodo alcohols 1e2 and prop-
argylic esters 3aek] to dihydropyrans/H-pyrans via regioselective
6-endo-trig cyclisation. The applicability of this pyran formation
protocol is then compared/contrasted with that of furan formation
by analogous phosphorus based substrates.4e
Scheme 3. Synthesis of
ester 24.
a
-formyl propargylic esters 21e23 and b-hydroxy propargylic
2.2. Cycloisomerisation of b-hydroxy propargylic esters
In the cycloisomerisation of compounds 4e20 and 24 leading to
pyran derivatives 25e42, initial trials were performed on 16 by
treating it with 2 mol % Ph3PAuCl/AgOTf in dichloromethane (Table
2). To our delight, the reaction using 16 led to 37 in 82% yield of the
isolated product (entry 1). Use of AgBF4 (entry 2) in place of AgOTf
reduced the time for completion of reaction from 6 h to 4 h and
increased the yield to 84%. By employing AgSbF6 as additive, the
reaction time was further reduced to 1 h and concomitantly, the
yield was still higher (90%; entry 3). In the absence of silver addi-
tives, no product formation was observed even after 12 h; AuCl or
AuCl3 as the gold component afforded lower yields after 12 h with
some starting material (w25%) remaining (entries 5 and 6). In the
absence of gold catalyst, AgSbF6 or AgBF4 (5 mol %) gave the
product in 78% or 68% yield (entries 7 and 8), respectively, in 6 h,
whereas AgOTf did not work well (entry 9). Other catalytic systems
were also less effective. Solvents like CH3CN, toluene, THF and di-
oxane along with 2% Ph3PAuCl/AgSbF6 led to poor yields (entries
13e16). Thus 2% Ph3PAuCl/AgSbF6 catalytic system in CH2Cl2 as the
solvent was the best condition (entry 3).
2. Results and discussion
2.1. Synthesis of propargylic ester precursors 4e24
2-Iodo-cyclohex-2-enol 1 and 2-iodo-cinnamyl alcohol 2 were
coupled with terminal propargylic esters 3aek for the synthesis of
b
-hydroxy propargylic esters (2-alkynyl allylic alcohols) 4e20. In
the case of 2-iodo-cyclohex-2-enol, the phosphine Ph3P was not
effective and hence (2-furyl)3P15 had to be used as the phosphine
component (Scheme 2, Table 1). Compounds 21e23 were syn-
thesised starting from 2-iodo-cinnamaldehyde16 and propargylic
esters 3bed (Scheme 3). The hydroxy propargylic ester 24 was
obtained by treating 22 with methyllithium.
R1
R2
Ph
OH
or
+
O
OH
I
O
I
R3
1
2
3a-k
Table 2
3 mol % PdCl2, 6 mol % R3P,
6 mol % CuI, Et3N, rt
Effect of catalyst/solvent in cycloisomerisation of 16
Ph
OH
OH
Ph
OH
or
Ph
BzO
37
O
Catalyst/ Solvent
rt
O
O
R = 2-furyl for 1
R1
R2
15-20
R1
R2
R3
O
= Ph
for 2
R3
O
OBz
4-14
16
Scheme 2. Synthesis of b-hydroxy propargylic esters 4e20.
Entry
Catalyst (mol %)
Solvent
Time (h)
Yield %a
1
2
3
4
5
6
7
8
2% Ph3PAuCl/AgOTf
2% Ph3PAuCl/AgBF4
2% Ph3PAuCl/AgSbF6
2% Ph3PAuCl
2% AuCl
2% AuCl3
5% AgSbF6
5% AgBF4
5% AgOTf
2% AuCl3/AgSbF6
2% AuCl/AgSbF6
1% Ph3PAuCl/AgSbF6
2% Ph3PAuCl/AgSbF6
2% Ph3PAuCl/AgSbF6
2% Ph3PAuCl/AgSbF6
2% Ph3PAuCl/AgSbF6
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Dioxane
THF
6
4
1
12
12
12
6
6
12
1
12
5
12
12
12
12
82
84
90
Table 1
No reactionb
Details on the synthesis of
b
-hydroxy propargylic esters 4e20
Traceb
Entry
Iodo-alcohol
Propargylic ester
Product, Yielda
52b
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
R1¼R2¼H, R3¼Ph (3a)
4, 70%
5, 86%
6, 81%
7, 76%
8, 81%
9, 80%
10, 62%
11, 84%
12, 66%
13, 72%
14, 73%
15, 82%
16, 84%
17, 88%
18, 81%
19, 82%
20, 92%
78
R1¼R2¼Me, R3¼Ph (3b)
68
(R1,R2)¼[eCH2e]5, R3¼Ph (3c)
(R1,R2)¼[eCH2e]4, R3¼Ph (3d)
R1¼Me, R2¼Et, R3¼Ph (3e)
R1¼R2¼Me, R3¼Me (3f)
9
18b
10
11
12
13
14
15
16
Complex mixture
42b
76
(R1,R2)¼[eCH2e]5, R3¼Me (3g)
R1¼R2¼Me, R3¼Et (3h)
10b
Traceb
20b
9
R1¼Me, R2¼i-Bu, R3¼Ph (3i)
R1¼Me, R2¼n-pentyl, R3¼Ph (3j)
R1¼R2¼n-propyl, R3¼Ph (3k)
R1¼R2¼H, R3¼Ph (3a)
Toluene
CH3CN
Traceb
10
11
12
13
14
15
16
17
a
Yield of the isolated product.
Starting material remained.
b
R1¼R2¼Me, R3¼Ph (3b)
(R1,R2)¼[eCH2e]5, R3¼Ph (3c)
(R1,R2)¼[eCH2e]4, R3¼Ph (3d)
R1¼Me, R2¼Et, R3¼Ph (3e)
R1¼R2¼Me, R3¼Me (3f)
The generality of the above reaction was checked against dif-
ferent substitutions on -hydroxy propargylic esters. The pre-
b
cursors 4e20 were successfully cycloisomerised to pyran
derivatives 25e41 (Table 3), respectively, in 64e90% yield.
a
Yield of the isolated product.

8004
R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
Table 3 (continued)
Similarly, precursor 24 (Table 3, entry 18) led to dihydropyran 42 in
86% yield. Among these products, 25 and 36 are 2H-pyrans, which
are synthesised from unsubstituted benzoates 4 and 15 (entries 1
and 12), whereas the rest are dihydropyrans. The structure of the
dihydropyran 27 was confirmed by X-ray crystallography (Fig. 1).
Entry
Substrate
Product, Yielda
10b
13
O
34, 82%
35, 81%
Table 3
BzO
BzO
Details on cycloisomerisation of
pyran derivatives 25e42
b
-hydroxy propargylic esters (4e20 and 24) to
n-Pentyl
n-Propyl
2 mol % Ph3PAuCl/
AgSbF6
R
OH
O
11
14
O
R
O
R
O
R1
R2
(or)
O
BzO
CH2Cl2, rt
n-Propyl
R1
R2
R3
R3
O
O
Ph
BzO
O
Entry
Substrate
Product, Yielda
12
13
14
15
16
17
36, 64%
37, 90%
38, 82%
1
2
4
25, 75%
26, 72%
O
Ph
BzO
O
O
BzO
BzO
Ph
BzO
5
6
O
Ph
BzO
O
15
18
39, 86%
O
3
27, 65% X-ray
BzO
Ph
BzO
O
O
16
17
19
20
40, 64%
41, 74%
4
7
O
28, 78%
29, 80%
30, 75%
31, 78%
Ph
AcO
BzO
BzO
5b
8
Ph
BzO
O
O
18
25
42, 86%
a
Yield of the isolated product.
Mixture of diastereomers.
b
6
9
O
OAc
AcO
O
7
10
8
11
12
O
32, 73%
EtOCO
BzO
O
9b
33, 78%
ꢀ
Fig. 1. ORTEP of compound 27. Selected bond lengths [A] with esd’s in parentheses:
O1eC9 1.433(3), C7eC8 1.318(3), O2eC7 1.411(3).
i-Bu

R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
8005
Our success in the above cycloisomerisation prompted us to
check the synthesis of phosphorus containing oxacycles.17 For
this purpose, we prepared (hydroxy)phosphonates18 43e45 from
Ph
OH
H+
Ph
-
OH
R2
LAu(I)
a
-formyl propargyl esters 21e22. Although these phosphono-
alkynols when treated with 3% Ph3PAuCl/AgSbF6 in di-
chloroethane did not react at 25 ꢀC, the reaction was complete in
3 h when heated at 70 ꢀC.4e Precursor 43 led to phosphono-pyran
46 (Scheme 4a), whereas 44 and 45 led to phosphono-furan 47
and phosphinoyl furan 48, respectively (Scheme 4b). However,
the yields in these cases are quantitative according to 31P NMR.
Additional peaks corresponding to phosphorus containing fu-
rans/pyrans were observed, but these products were not isolated.
It is to be noted that in the phosphono-furans, the benzoyloxy
group has been eliminated as benzoic acid leading to the cyclo-
alkenic double bond at the corresponding site. Thus an in-
teresting variation in the product formation is observed with
these phosphono-alkynol precursors.19
ZO
R1
R1
OZ
R2
LAu(I)
IV
Ph
O
Protodeauration
R1
Ph
O
R1
ZO
R2
ZO
LAu
R2
H
V
Scheme 5. Proposed reaction pathway for the formation of pyran.
There appears to be some subtle steric/electronic factors in-
volved here. We found that -hydroxy propargylic esters 49e50
b
O
O
underwent self-condensation via nucleophilic substitution20 of
ester group to afford 12-membered macrocycles 51(a,b)e52, re-
spectively (Scheme 6). The isomerism may be due to the different
conformations (or disposition of substituents) of the cyclohexyl
rings in 51a,b; such a possibility does not arise in the case of 52. In
the absence of the catalyst, the reaction using 49 did not give the
cyclised products 51a,b. In addition to the steric/electronic factors,
perhaps, the oxophilicity of gold(I) complex20c,d might have driven
the condensation. Two isomers 51a,b were formed (and separated)
in the reaction using 49, the geometry of 51b was confirmed by X-
ray crystallography (Fig. 2). These products could be attractive
substrates for cycloaddition reactions. Although this condensation
is interesting, it is not the main theme of the present work and
hence is not elaborated in this study.
O
P
O
Ph
OH
O
O
P
a)
Conditions
Ph
BzO
O
Me
Me
Me
Me
OBz
43
46, 44 %
R
O
R
R
P
O
R
P
Ph
OH
b)
Conditions
Ph
O
OBz
R
R
44-45
(R,R) = OCH2CMe2CH2O (47, 62 %)
R = Ph (48, 28 %)
2 mol % Ph3PAuCl/
AgSbF6
Ph
OH
O
Ph
O
Conditions: 3 mol % Ph3PAuCl/ AgSbF6, DCE, 70 oC, 3 h
CH2Cl2, rt
R
R
Ph
R
O
Scheme 4. Synthesis and cyclisation of phosphono-alkynols to phosphono-furans or
R1
O
phosphono-pyrans.
R
(RR) = [-CH2-]5, R1 = Me 49
R = Me, R1 = Et
50
51a (28%) + 51b [X-ray, 44% ]
52 (60%)
We propose that the reaction leading to pyrans proceeds via
Scheme 6. Formation of macrocycles from
b-hydroxy propargylic esters.
Au(I) catalysed
p-activation of propargylic ester, which undergoes
1,3-carboxylate migration11 to form allene intermediate IV
(Scheme 5) followed by regioselective hydroxyl group addition to
allene, which is 6-endo-trig cyclisation affording the six-membered
oxacycle V. Subsequently, V undergoes proto-deauration to lead to
pyran derivative.11,14 The reaction also occurs with silver salts, al-
beit less effectively, due to the strong electron withdrawing nature
(of the groups) in counter anions. The softness of silver also plays
a role in coordinating with the alkyne moiety and hence an Ag(I)
intermediate similar to IVeV is feasible.1c With regard to the
cycloisomerisation of phosphono-alkynols to phosphono-pyrans,
the reaction pathway is analogous to the above, whereas the for-
mation of phosphono-furans has occurred differently.4e The reason
for the difference in reactivity between the non-phosphorus
alkynols and phosphorus-containing alkynols is probably a conse-
quence of the electron withdrawing nature of the phosphoryl
group.
ꢀ
Fig. 2. ORTEP of compound 51b. Selected bond lengths [A] with esd’s in parentheses:
(Hydrogens are omitted for clarity) O1eC1 1.437(3) and O2eC18 1.443(3).

8006
R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
3. Conclusions
Yield 1.33 g (86%); Colourless oil; [Found: C, 78.76; H, 8.15. C16H20O2
requires C, 78.65; H, 8.25%]; Rf (2% EtOAc/hexane) 0.40; IR (neat,
cmꢁ1) 3304, 3069, 2959, 2932, 2877, 2121, 1726, 1606, 1447, 1277,
1118, 1096, 1025, 948, 712; dH (400 MHz, CDCl3) 8.03e7.42 (5H, m),
2.62 (1H, s), 2.17e2.12 and 2.04e1.98 (4H, m), 1.61e1.53 (4H, m),
0.98 (3H, t, J¼7.4 Hz); dC (100.6 MHz, CDCl3) 164.7, 132.8, 130.9,
129.5, 128.3, 83.3, 79.0, 74.2, 40.6, 17.4, 14.1; LC/MS m/z 245 [Mþ1]þ.
In summary, various pyran derivatives have been synthesised
from
b-hydroxy propargylic esters via 1,3-carboxylate migration
(leading to allenic intermediates) followed by regioselective cycli-
sation. The method utilises a wide range of easily accessible pre-
cursors, and demonstrates general and highly efficient route for
a variety of substituted pyrans under mild conditions in short re-
action time. Phosphorus containing hydroxy propargyl esters led to
phosphono-furans as well as phosphono-pyrans under the same
catalytic system. During this investigation it is also shown that, in
a few cases, the electronic factors compelled the dimerisation of
propargylic esters via nucleophilic substitution to form 12-
membered macrocycles, indicating a different reactivity pattern
of the precursors.
4.3. Synthesis of
b-hydroxy propargylic esters 4e14
The procedure available in the literature4b was modified in this
case. To mixture of 2-iodocyclohex-2-enol (1) (400 mg,
a
1.80 mmol), PdCl2 (10 mg, 0.03 mol equiv), (furyl)3P (25 mg,
0.06 equiv) and CuI (21 mg, 0.06 equiv) in triethylamine (6 mL) was
added the appropriate alkyne among 3aek (2.4 mmol, 1.5 equiv)
through a micropipette. The contents were stirred for 6 h at rt. The
reaction mixture was filtered and the solvent removed in vacuum.
The crude product was purified by column chromatography using
silica gel with EtOAc/hexane mixture as the eluent.
4. Experimental section
4.1. General
Solvents were dried according to known methods as appropri-
ate.21 1H, 13C and 31P NMR spectra (1H, 400 MHz; 13C, 100.6 MHz;
31P, 162 MHz) were recorded using a 400 MHz spectrometer in
4.3.1. 3-(6-Hydroxycyclohex-1-enyl)prop-2-ynyl benzoate 4. Yield
0.325 g (70%); Gummy liquid; [Found: C, 74.85; H, 6.21. C16H16O3
requires C, 74.98; H, 6.29%]; Rf (20% EtOAc/hexane) 0.40; IR (neat,
cmꢁ1) 3443, 3061, 2946, 2870, 2300 (w), 2230, 1728, 1603, 1580,
1453, 1271, 1109, 739; dH (400 MHz, CDCl3) 8.08e7.42 (5H, m), 6.29
(1H, t, J¼4.0 Hz), 5.06 (2H, s), 4.19 (1H, br s), 2.19e1.57 (6H, m); dC
(100.6 MHz, CDCl3) 166.0, 139.1, 133.3, 129.8, 129.5, 128.3, 123.3,
85.9, 82.8, 66.6, 53.4, 30.6, 25.9, 17.9; LC/MS m/z 257 [Mþ1]þ.
CDCl3 with shifts referenced to SiMe4 (d 0) or 85% H3PO4 (d 0). IR
spectra were recorded on an FTIR spectrophotometer. Melting
points were determined by using a local hot-stage melting point
apparatus and are uncorrected. Elemental analyses were carried
out on a PerkineElmer 240C CHN or Thermo Finnigan EA1112 CHNS
analyzer from School of Chemistry, University of Hyderabad,
Hyderabad. Mass spectra were recorded using LC/MS and HRMS
(ESI-TOF analyzer) equipment.
4.3.2. 4-(6-Hydroxycyclohex-1-enyl)-2-methylbut-3-yn-2-yl benzo-
ate 5. Yield 0.437 g (86%); Gummy liquid; [Found: C, 76.13; H, 7.15.
C18H20O3 requires C, 76.03; H, 7.09%]; Rf (20% EtOAc/hexane) 0.40;
IR (neat, cmꢁ1) 3470, 3063, 2986, 2940, 2868, 2300 (vw), 2220 (w),
1719, 1603, 1584, 1283, 1107, 714; dH (400 MHz, CDCl3) 8.03e8.01
and 7.56e7.40 (5H, m), 6.16 (1H, t, J¼3.8 Hz), 4.21e4.20 (1H, m),
2.11e1.96 (2H, m), 1.82 (6H, s), 1.79e1.55 (4H, m); dC (100.6 MHz,
CDCl3) 165.4, 136.5, 132.9, 130.9, 129.7, 128.3, 124.4, 91.1, 83.6, 73.1,
67.2, 30.3, 29.2, 29.0, 25.8, 19.0; LC/MS m/z 285 [Mþ1]þ.
Precursors 1,22 24e,16 and 3aeg3jel,23 are known.
4.2. Synthesis of propargylic esters 3hek
4.2.1. 2-Methylbut-3yn-2yl propionate 3h. This compound was
synthesised by following a literature procedure24a by using 2-
methylbut-3-yn-2ol (0.864 g, 10.3 mmol), propionyl chloride
(1.80 mL, 20.6 mmol), DMAP (0.379 g, 3.1 mmol) and pyridine
(8.3 mL) in CH2Cl2 (40 mL). Yield 1.44 g (85%); Colourless oil;
[Found: C, 68.54; H, 8.63. C8H12O2 requires C, 68.46; H, 8.71%]; IR
(neat, cmꢁ1) 3293, 3058, 2986, 2937, 2290, 2247, 1734, 1425, 1266,
1195, 1134, 1085, 1041; dH (400 MHz, CDCl3) 2.53 (1H, s), 2.30 (2H,
qrt, J¼7.8 Hz), 1.67 (6H, s), 1.13 (3H, t, J¼7.4 Hz); dC (100.6 MHz,
4.3.3. 1-((6-Hydroxycyclohex-1-enyl)ethynyl)cyclohexyl
benzoate
6. Yield 0.473 g (81%); Gummy liquid; [Found: C, 77.63; H, 7.36.
C21H24O3 requires C, 77.75; H, 7.46%]; Rf (20% EtOAc/hexane) 0.40;
IR (neat, cmꢁ1) 3519, 2936, 2861, 2218, 1721, 1601, 1451, 1283, 1250,
1109, 914, 712; dH (400 MHz, CDCl3) 8.05e7.41 (5H, m), 6.17 (1H, t,
J¼4.2 Hz), 4.20 (1H, t, J¼5.4 Hz), 1.98e2.21 and 1.45e1.80 (16H, m);
dC (100.6 MHz, CDCl3) 165.2, 136.4, 132.9, 131.1, 129.7, 128.3, 124.6,
90.3, 85.3, 76.5, 67.3, 37.3, 30.3, 25.8, 25.2, 22.6, 19.1; LC/MS m/z 325
[Mþ1]þ.
CDCl3)
d 172.5, 84.7, 72.1, 71.2, 28.8, 28.0, 8.8; LC/MS m/z 141
[Mþ1]þ.
4.2.2. 3,5-Dimethylhex-1-yn-3-yl benzoate 3i. This compound was
obtained by desilylation of VI (see Supplementary data) (1.40 g,
4.6 mmol) using a literature procedure.24b Yield 0.953 g (90%, col-
ourless oil). The spectral data are in accordance with the literature
report.3h
4.3.4. 1-((6-Hydroxycyclohex-1-enyl)ethynyl)cyclopentyl benzoate
7. Yield 0.426 g (76%); Gummy liquid; Rf (20% EtOAc/hexane) 0.40;
IR (neat, cmꢁ1) 3467, 2939, 2867, 2215, 1950 (w), 1713, 1599, 1444,
1273, 1164, 1102, 962, 709; dH (400 MHz, CDCl3) 8.02e7.40 (5H, m),
6.15 (1H, t, J¼4.0 Hz), 4.19 (1H, t, J¼6.2 Hz), 2.44e2.41, 2.27e2.01,
1.99e1.93, 1.85e1.72 and 1.67e1.55 (14H, m); dC (100.6 MHz, CDCl3)
165.6, 136.5, 133.0, 130.0, 129.7, 128.3, 124.5, 90.3, 84.2, 81.8, 67.1,
40.6, 30.3, 25.8, 23.5, 18.9; HRMS (ESI): [MþþNa], found 333.1466.
C20H22NaO3 requires 333.1467.
4.2.3. 3-Methyloct-1-yn-3yl benzoate 3j. This compound was ob-
tained by desilylation VII (2.00 g, 6.3 mmol) in a manner similar to
that for 3i. Yield 1.37 g (89%); Colourless oil; Rf (2% EtOAc/hexane)
0.40; IR (neat, cmꢁ1) 3304, 3260, 2953, 2932, 2871, 2121,1726,1606,
1447, 1375, 1271,1178, 1156, 1107, 1074,1030, 882, 718; dH (400 MHz,
CDCl3) 8.03e7.42 (5H, m), 2.61 (1H, s), 2.11e1.95 (2H, m), 1.82 (3H,
s), 1.65e1.57 and 1.38e1.35 (6H, m), 0.93 (3H, t, J¼6.8 Hz); dC
(100.6 MHz, CDCl3) 164.9, 1361, 132.9, 131.0, 129.6, 128.4, 84.0, 75.6,
73.5, 41.7, 31.8, 26.6, 23.9, 22.6, 14.1; HRMS (ESI): [MþþNa], found
267.1362. C16H20NaO2 requires 267.1361.
4.3.5. 1-(6-Hydroxycyclohex-1-enyl)-3-methylpent-1-yn-3-yl ben-
zoate 8: (mixture of diastereomers). Yield 0.435 g (81%); Gummy
liquid; Rf (20% EtOAc/hexane) 0.40; IR (neat, cmꢁ1) 3482, 2980,
2933, 2876, 2213, 1721, 1447, 1281, 1105, 1022, 717; dH (400 MHz,
CDCl3) 8.03e7.41 (10H, m), 6.17 (2H, br s), 4.23 and 4.19 (2H, two br
s), 3.13 (2H, s), 2.15e1.81 and 1.76e1.54 (22H, m), 1.15e1.10 (6H, m);
dC (100.6 MHz, CDCl3) 165.5, 165.3, 136.5, 136.2, 132.9, 131.0, 129.6,
4.2.4. 4-Ethynylheptan-4-yl benzoate 3k. This compound was ob-
tained by desilylation VIII (2.00 g, 6.3 mmol) as described for 3i.

R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
8007
128.3, 124.5, 90.0, 84.7, 76.8, 67.3, 67.2, 34.9, 34.7, 30.3, 26.3, 25.8,
19.0, 8.8; HRMS (ESI): [MþþNa], found 321.1465. C19H22NaO3 re-
quires 321.1467.
41.0, 40.9, 30.3, 25.8, 19.1, 17.70, 17.65, 14.3; HRMS (ESI): [MþþNa],
found 363.1937. C22H28NaO3 requires 363.1936.
4.4. Synthesis of b-hydroxy propargylic esters 15e20
4.3.6. 4-(6-Hydroxycyclohex-1-enyl)-2-methylbut-3-yn-2-yl acetate
9. Yield 0.320 g (80%); Gummy liquid; [Found: C, 70.15; H, 8.23.
C13H18O3 requires C, 70.24; H, 8.16%]; Rf (20% EtOAc/hexane) 0.40;
IR (neat, cmꢁ1) 3470, 2988, 2940, 2870, 2300 (vw), 2224, 1734,
1672, 1368, 1271, 1244, 1129, 1017; dH (400 MHz, CDCl3) 6.15 (1H, t,
J¼3.8 Hz), 4.17 (1H, t, J¼6.2 Hz), 2.86 (1H, br s), 2.13e2.08 (2H, m),
1.99e1.93 and 1.79e1.72 (2H, m), 2.02 (3H, s), 1.66 (6H, s),
1.65e1.62 (2H, m); dC (100.6 MHz, CDCl3) 169.9, 136.5, 124.3, 90.9,
83.2, 72.4, 67.0, 30.2, 29.0, 28.8, 25.7, 22.0, 18.8; LC/MS m/z 223
[Mþ1]þ.
A literature procedure4b was slightly modified. To a mixture of
(Z)-2-iodo-3-phenylprop-2-en-1ol 2 (400 mg, 1.54 mmol), PdCl2
(8 mg, 0.03 mol equiv), PPh3 (21 mg, 0.06 mol equiv) and CuI
(18 mg, 0.06 mol equiv) in triethylamine (5 mL) was added the
appropriate alkyne among 3aef (1.5 equiv). The contents were
stirred for 6 h at rt. The reaction mixture was filtered and the sol-
vent removed in vacuum. The crude product was purified by col-
umn chromatography using silica gel with EtOAc/hexane (1:5)
mixture as eluent.
4.3.7. 1-((6-Hydroxycyclohex-1-enyl)ethynyl)cyclohexyl
acetate
4.4.1. (E)-4-(Hydroxymethyl)-5-phenylpent-4-en-2-ynyl
benzoate
10. Yield 0.294 g (62%); Gummy liquid; [Found: C, 73.16; H, 8.35.
C16H22O3 requires C, 73.25; H, 8.45%]; Rf (20% EtOAc/hexane) 0.40;
IR (neat, cmꢁ1) 3468, 2938, 2863, 2218,1740,1768,1449,1269,1233,
1020; dH (400 MHz, CDCl3) 6.16 (1H, t, J¼4.0 Hz), 4.18 (1H, t,
J¼6.4 Hz), 2.90 (1H, br s), 2.13e2.07 (4H, m), 2.04 (3H, s), 1.84e1.28
(12H, m); dC (100.6 MHz, CDCl3) 169.9, 136.3, 124.6, 90.2, 85.1, 76.0,
67.3, 37.2, 37.0, 30.3, 25.8, 25.2, 22.7, 22.1, 19.0; LC/MS m/z 263
[Mþ1]þ.
15. Yield 0.369 g (82%); Gummy liquid; [Found: C, 77.93; H, 5.61.
C19H16O3 requires C, 78.06; H, 5.52%]; Rf (20% EtOAc/hexane) 0.35;
IR (neat, cmꢁ1) 3439, 3063, 3030, 2928, 2859, 2216, 1725, 1601,
1493, 1451, 1269, 1107, 758, 712; dH (400 MHz, CDCl3) 8.12e7.29
(10H, m), 6.84 (1H, s), 5.17 (1H, s), 4.32 (1H, s); dC (100.6 MHz,
CDCl3) 166.0, 135.6, 135.5, 133.4, 129.9, 129.6, 128.8, 128.6, 128.5,
128.4, 120.3, 90.9, 84.6, 67.1, 53.5; LC/MS m/z 293 [Mþ1]þ.
4.4.2. (E)-5-(Hydroxymethyl)-2-methyl-6-phenylhex-5-en-3-yn-2-yl
benzoate 16. Yield 0.414 g (84%); Gummy liquid; [Found: C, 78.65;
H, 6.36. C21H20O3 requires C, 78.73; H, 6.29%]; Rf (20% EtOAc/hex-
ane) 0.35; IR (neat, cmꢁ1) 3434, 3063, 3027, 2986, 2934, 2865, 2207,
1968, 1723, 1451, 1281, 1105, 1026, 756, 714, 693; dH (400 MHz,
CDCl3) 8.06e7.28 (10H, m), 6.73 (1H, s), 4.29 (2H, s), 2.53 (1H, s),
1.90 (6H, s); dC (100.6 MHz, CDCl3) 165.3, 135.8, 134.1, 133.1, 130.8,
129.7, 128.7,128.4,128.2,121.1, 98.4, 82.5, 73.1, 67.3, 29.0; LC/MS m/z
321 [Mþ1]þ.
4.3.8. 4-(6-Hydroxycyclohex-1-enyl)-2-methylbut-3-yn-2-yl
pro-
pionate 11. Yield 0.360 g (84%); Gummy liquid; [Found: C, 71.23; H,
8.45. C14H20O3 requires C, 71.16; H, 8.53%]; Rf (20% EtOAc/hexane)
0.40; IR (neat, cmꢁ1) 3478, 2986, 2942, 2874, 2350 (w), 2220, 1732,
1628, 1462, 1362, 1275, 1190, 1129, 1080, 997; dH (400 MHz, CDCl3)
6.14 (1H, t, J¼4.0 Hz), 4.17 (1H, br s), 2.95 (1H, br s), 2.29 (2H, qrt,
J¼7.6 Hz), 2.11e1.68 (12H, m), 1.11 (3H, t, J¼7.4 Hz); dC (100.6 MHz,
CDCl3) 173.6, 136.4, 124.5, 91.3, 83.1, 72.2, 67.2, 30.3, 29.1, 28.9, 28.4,
25.8, 19.0, 9.0; LC/MS m/z 237 [Mþ1]þ.
4.4.3. (E)-1-(3-(Hydroxymethyl)-4-phenylbut-3-en-1-ynyl)cyclo-
hexyl benzoate 17. Yield 0.488 g (88%); Gummy liquid; [Found: C,
79.85; H, 6.63. C24H24O3 requires C, 79.97; H, 6.71%]; Rf (20% EtOAc/
hexane) 0.35; IR (neat, cmꢁ1) 3468, 3068, 3025, 2931, 2860, 2197,
1704, 1600, 1452, 1288, 1184, 1118, 1074, 910, 756, 707; dH (400 MHz,
CDCl3) 8.08e7.24 (10H, m), 6.72 (1H, s), 4.29 (2H, s), 2.72 (1H, s),
2.35e2.12 (4H, m), 1.77e1.45 (6H, m); dC (100.6 MHz, CDCl3) 165.1,
135.8, 133.6, 133.0, 130.8, 129.6, 128.6, 128.3, 128.2, 128.1, 121.3, 97.5,
84.3, 76.5, 67.1, 37.0, 25.1, 22.6; LC/MS m/z 361 [Mþ1]þ.
4.3.9. 1-(6-Hydroxycyclohex-1-enyl)-3,5-dimethylhex-1-yn-3-yl
benzoate 12 (two diastereomers). Yield 0.385 g (66%); Gummy liq-
uid; Rf (20% EtOAc/hexane) 0.40; IR (neat, cmꢁ1) 3485, 3069, 2959,
2850, 2219, 1710, 1606, 1452, 1277, 1107, 1025, 712; dH (400 MHz,
CDCl3) 8.02e8.00 and 7.57e7.40 (10H, m), 6.17e6.14 (2H, m), 4.23
and 4.18 (2H, two t, J¼6.2 and 6.0 Hz, respectively), 3.13 (2H, br s),
2.13e1.96, 1.90e1.74 and 1.66e1.61 (24H, m), 1.03e1.09 (12H, m); dC
(100.6 MHz, CDCl3) 165.6, 165.4, 136.6, 136.2, 133.0, 131.0, 130.2,
129.7, 128.5, 128.4, 124.4, 90.4, 84.9, 76.4, 67.2, 50.0, 49.8, 30.2, 27.5,
27.3, 25.8, 25.1, 24.2, 24.1, 19.0; HRMS (ESI): [MþþNa], found
349.1780. C21H26NaO3 requires 349.1780.
4.4.4. (E)-1-(3-(Hydroxymethyl)-4-phenylbut-3-en-1-ynyl)cyclo-
pentyl benzoate 18. Yield 0.435 g (81%); Gummy liquid; Rf (20%
EtOAc/hexane) 0.35; IR (neat, cmꢁ1) 3436, 3063, 2960, 2867, 2220
(w), 1980 (w), 1718, 1599, 1444, 1278, 1107, 1030; dH (400 MHz,
CDCl3) 8.04e7.24 (10H, m), 6.72 (1H, s), 4.28 (2H, s), 2.51e2.31 and
1.89e1.85 (8H, m), 1.02 (1H, t, J¼7.2 Hz); dC (400 MHz, CDCl3) 165.5,
135.8, 133.9, 133.1, 130.6, 129.7, 128.6, 128.4, 128.3, 128.2, 121.3, 97.7,
83.1, 81.7, 67.2, 40.4, 23.5; HRMS (ESI): [MþþNa], found 369.1466.
C23H22NaO3 requires 369.1467.
4.3.10. 1-(6-Hydroxycyclohex-1-enyl)-3-methyloct-1-yn-3-yl benzo-
ate 13 (two diastereomers). Yield 0.438 g (72%); Gummy liquid;
[Found: C, 77.52; H, 8.15. C22H28O3 requires C, 77.61; H, 8.29%]; Rf
(20% EtOAc/hexane) 0.40; IR (neat, cmꢁ1) 3493, 3058, 2939, 2867,
2215, 1713, 1604, 1449, 1273, 1107, 1024, 719; dH (400 MHz, CDCl3)
8.01e7.27 (10H, m), 6.17 and 6.16 (2H, two br s), 4.23 and 4.18 (2H,
two br s), 2.10e1.90, 1.80e1.74 and 1.64e1.54 (26H, m), 1.36 (8H, br
s), 0.92 (6H, br s); dC (100.6 MHz, CDCl3) 165.5, 165.4, 136.6, 136.2,
132.9, 131.0, 129.7, 128.3, 124.5, 90.3, 84.61, 84.60, 76.8, 76.4, 67.3,
67.2, 41.8, 41.6, 31.8, 30.2, 26.80, 26.75, 25.8, 24.03, 24.00, 22.6, 19.0,
14.1; LC/MS m/z 341 [Mþ1]þ.
4.4.5. (E)-6-(Hydroxymethyl)-3-methyl-7-phenylhept-6-en-4-yn-3-
yl benzoate 19. Yield 0.440 g (82%); Gummy liquid; Rf (20% EtOAc/
hexane) 0.35; IR (neat, cmꢁ1) 3446, 3058, 2970, 2934, 2877, 2220
(w), 1723, 1495, 1444, 1268, 1107, 1066, 1024, 714; dH (400 MHz,
CDCl3) 8.06e7.26 (10H, m), 6.72 (1H, s), 4.30 (2H, s), 2.62 (1H, s),
2.23e2.03 (2H, m), 1.88 (3H, s), 1.17 (1H, t, J¼7.4 Hz); dC (100.6 MHz,
CDCl3) 165.3, 135.8, 133.9, 133.0, 130.9, 129.6, 128.6, 128.4, 128.3,
128.2, 121.3, 97.5, 83.6, 76.8, 67.3, 34.7, 26.1, 8.8; HRMS (ESI):
[MþþNa], found 357.1468. C22H22NaO3 requires 357.1467.
4.3.11. 4-((6-Hydroxycyclohex-1-enyl)ethynyl)heptan-4-yl benzoate
14. Yield 0.445 g (73%); Gummy liquid; Rf (20% EtOAc/hexane)
0.40; IR (neat, cmꢁ1) 3485, 2970, 2926, 2866, 2214,1715,1606,1452,
1277, 1112, 1025, 712; dH (400 MHz, CDCl3) 8.01e7.40 (5H, m), 6.16
(1H, t, J¼3.6 Hz), 4.21 (1H, br s), 3.16 (1H, br s), 2.14e1.95 and
1.78e1.48 (14H, m), 0.98 (6H, t, J¼7.0 Hz); dC (100.6 MHz, CDCl3)
165.4, 136.2, 132.9, 131.1, 129.7, 128.4, 124.6, 89.6, 85.5, 79.7, 67.3,
4.4.6. (E)-5-(Hydroxymethyl)-2-methyl-6-phenylhex-5-en-3-yn-2-yl
acetate 20. Yield 0.368 g (92%); Gummy liquid; [Found: C, 74.21; H,

8008
R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
7.13. C16H18O3 requires C, 74.39; H, 7.02%]; Rf (20% EtOAc/hexane)
0.35; IR (neat, cmꢁ1) 3426, 3058, 3025, 2988, 2936, 2865, 2215,
1740, 1600, 1495, 1447, 1368, 1244, 1129, 1019, 756, 694; dH
(400 MHz, CDCl3) 7.83e6.72 (6H, m), 4.27 (1H, s), 2.06 (3H, s), 1.74
(6H, s); dC (100.6 MHz, CDCl3) 169.9, 135.8, 134.0, 128.6, 128.3, 128.1,
121.1, 98.2, 82.1, 72.4, 67.0, 28.8, 22.0; LC/MS m/z 259 [Mþ1]þ.
(3H, d, J¼7.2 Hz); dC (100.6 MHz, CDCl3) 165.1, 135.9, 133.0, 132.8,
131.0, 129.7, 128.8, 128.3, 128.2, 126.0, 98.2, 83.5, 76.6, 72.4, 37.1,
25.2, 23.1, 22.7; LC/MS m/z 377 [Mþ1]þ.
4.7. General procedure for the synthesis of pyrans derivatives
25e42
4.5. Synthesis of
a
-formyl propargylic esters 21e23
To a solution of one of the hydroxyl propargylic esters [4e20 or
24; 0.5 mmol] in dry dichloromethane (DCM; 1 mL) was added
a solution of Ph3PAuCl (0.02 equiv) and AgSbF6 (0.02 equiv) in DCM
(1 mL). The contents were stirred at room temperature (25 ꢀC) till
the starting material was consumed. The solvent was removed
under vacuum and crude product was purified by column chro-
matography using silica gel with ethyl acetate/hexane mixture as
eluent to afford the corresponding product among 25e42.
A literature procedure4b was modified. To a mixture of (Z)-2-
iodo-3-phenyl acraldehyde16 (500 mg, 1.94 mmol), PdCl2 (10 mg,
0.03 mol equiv), (furyl)3P (28 mg, 0.06 mol equiv), CuI (23 mg,
0.06 mol equiv) and diisopropylamine (0.9 mL, 3.0 mol equiv) in
THF (6 mL) was added the corresponding alkyne 3bed (1.5 mol
equiv). The contents were stirred for 6 h at rt. The reaction mixture
was filtered and the solvent removed by vacuum. The crude
product was purified by column chromatography using silica gel
with EtOAc/hexane mixture as eluent.
4.7.1. 5,6,7,8-Tetrahydro-2H-chromen-4-yl benzoate 25. Yield 0.0
96 g (75%); Gummy liquid; Rf (1% EtOAc/hexane) 0.30; IR (neat,
cmꢁ1) 2930, 2857, 1721, 1603, 1524, 1375, 1177, 1098, 1026, 941, 666;
dH (400 MHz, CDCl3) 8.08e7.41 (5H, m), 6.29 (1H, s), 5.25 (2H, s),
2.62e2.40 and 1.87e1.71 (8H, m); dC (100.6 MHz, CDCl3) 166.5,
152.0, 147.0, 133.1, 129.9, 128.4, 118.0, 112.1, 59.1, 23.3, 23.1, 23.0,
22.1; HRMS (ESI): [MþþNa], found 279.0998. C16H16NaO3 requires
m/z 279.0997.
4.5.1. (E)-5-Formyl-2-methyl-6-phenylhex-5-en-3-yn-2-yl benzoate
21. Yield 0.525 g (85%); White solid; Mp 64e66 ꢀC; Rf (10% EtOAc/
hexane) 0.35; IR (KBr, cmꢁ1) 3069, 2981, 2833, 2250 (vw), 1726,
1682, 1589, 1452, 1277, 1145, 1096, 910, 712, 690; dH (400 MHz,
CDCl3) 9.57 (1H, s), 8.13e7.37 (11H, m), 1.96 (6H, s); dC (100.6 MHz,
CDCl3) 191.0, 164.9, 152.2, 133.8, 133.0, 131.7, 130.9, 130.8, 129.7,
128.7, 128.4, 121.9, 101.8, 78.2, 72.9, 29.0; HRMS (ESI): [MþþNa],
found 341.1156. C21H18NaO3 requires 341.1154.
4.7.2. 2,2-Dimethyl-6,7,8,8a-tetrahydro-2H-chromen-4-yl benzoate
26. Yield 0.102 g (72%); Gummy liquid; [Found: C, 76.12; H, 7.15.
C18H20O3 requires C, 76.03; H, 7.09%]; Rf (1% EtOAc/hexane) 0.30; IR
(neat, cmꢁ1) 3065, 2976, 2938, 2868, 1738, 1601, 1453, 1381, 1316,
1265, 1208, 1177, 1109, 1090, 1069, 1026, 710; dH (400 MHz, CDCl3)
8.14e7.47 (5H, m), 5.73 (1H, br s), 5.54 (1H, s), 4.48 (1H, br s),
2.14e1.60 (6H, m), 1.44 and 1.40 (6H, two s); dC (100.6 MHz, CDCl3)
164.7, 142.0, 133.5, 130.0, 128.6, 122.8, 121.4, 72.7, 67.7, 30.1, 29.3,
25.5, 25.3, 20.7; LC/MS m/z 285 [Mþ1]þ.
4.5.2. (E)-1-(3-Formyl-4-phenylbut-3-en-1-ynyl)cyclohexyl benzoate
22. Yield 0.570 g (82%); Gummy liquid; Rf (10% EtOAc/hexane) 0.35;
IR (neat, cmꢁ1) 3057, 2937, 2860, 2350 (w), 1721, 1688, 1600, 1452,
1310, 1277, 1249, 1107, 1019, 712; dH (400 MHz, CDCl3) 9.58 (1H, s),
8.15e8.09 and 7.60e7.35 (11H, m), 2.40e1.79 and 1.69e1.43 (10H,
m); dC (100.6 MHz, CDCl3) 191.0, 164.7, 155.7, 155.6, 133.9, 133.0,
131.7, 131.0, 129.7, 128.7, 128.4, 122.2, 101.4, 80.3, 76.4, 25.3, 22.7;
HRMS (ESI): [MþþNa], found 381.1465. C24H22NaO3 requires
381.1467.
4.7.3. 6,7,8,8a-Tetrahydrospiro[chromene-2,10-cyclohexane]-4-yl
benzoate 27. Yield 0.105 g (65%); White solid; Mp 54e56 ꢀC; Rf (1%
EtOAc/hexane) 0.30; IR (KBr, cmꢁ1) 3063, 2932, 2859, 1738, 1665,
1632, 1601, 1451, 1391, 1264, 1171, 1088, 914, 708; dH (400 MHz,
CDCl3) 8.15e8.12 and 7.63e7.47 (5H, m), 5.70 (s), 5.62 (1H, s), 4.46
(1H, br s), 2.13e1.47 (16H, m); dC (100.6 MHz, CDCl3) 164.6, 142.4,
133.5, 130.2, 130.0, 129.5, 128.6, 128.3, 122.1, 121.0, 73.5, 66.9, 38.4,
33.5, 29.3, 25.6, 25.3, 21.9, 21.7, 20.7; HRMS (ESI): [MþþH], found
325.1803. C21H25O3 requires 325.1803. X-ray structure was de-
termined for this compound.
4.5.3. (E)-1-(3-Formyl-4-phenylbut-3-en-1-ynyl)cyclopentyl benzo-
ate 23. Yield 0.610 g (91%); White solid; Mp 76e78 ꢀC; Rf (10%
EtOAc/hexane) 0.35; IR (KBr, cmꢁ1) 3074, 2964, 2849, 1715, 1682,
1589, 1447, 1282, 1235, 1107, 761; dH (400 MHz, CDCl3) 9.55 (1H, s),
7.59e7.33 and 8.12e8.08 (11H, m), 2.57e2.41 and 1.90e1.86 (8H,
m); dC (100.6 MHz, CDCl3) 190.9, 165.1, 151.9, 133.8, 133.0, 131.6,
130.8, 130.6, 129.6, 128.6, 128.4, 122.0, 101.5, 81.4, 78.8, 40.5, 23.5;
HRMS (ESI): [MþþNa], found 367.1310. C23H20NaO3 requires
367.1310.
4.7.4. 6,7,8,8a-Tetrahydrospiro[chromene-2,10-cyclopentane]-4-yl
benzoate 28. Yield 0.122 g (78%); Gummy liquid; Rf (1% EtOAc/
hexane) 0.30; IR (neat, cmꢁ1) 3047, 2951, 2855, 1732, 1663, 1594,
1444, 1263, 1168, 1066, 1029, 811, 710; dH (400 MHz, CDCl3)
8.14e8.12 and 7.63e7.47 (5H, m), 5.72 (1H, br s), 5.55 (1H, s), 4.35
(1H, br s), 2.13e2.04 and 1.94e1.58 (14H, m); dC (100.6 MHz, CDCl3)
164.7, 142.1, 133.5, 130.1, 129.9, 129.5, 128.6, 121.9, 121.2, 83.5, 68.5,
40.8, 36.4, 29.3, 25.3, 24.3, 24.1, 20.7; HRMS (ESI): [MþþNa], found
333.1468. C20H22NaO3 requires 333.1467.
4.6. Synthesis of (E)-1-(3-benzylidene-4-hydroxypent-1-ynyl)
cyclohexyl benzoate 24
A literature procedure25 was modified. To a stirred solution of
(E)-1-(3-formyl-4phenylbut-3-en-1ynyl)cyclohexyl benzoate 22
(400 mg, 1.1 mmol) in THF (8 mL) was added 1.6 M CH3Li (0.75 mL,
1.0 mol equiv) slowly at ꢁ78 ꢀC. The reaction mixture was allowed
to reach rt while stirring and then quenched with saturated NH4Cl
solution (10 mL). Et2O (20 mL) was added and the organic layer was
washed with brine solution (20 mL), dried over anhyd Na2SO4 and
concentrated. Compound 24 was separated from the crude by
column chromatography using silica gel with ethyl acetate/hexane
mixture as the eluent. Yield 0.194 g (46%, gummy liquid); [Found: C,
79.86; H, 7.45. C25H28O3 requires C, 79.75; H, 7.50%]; Rf (20% EtOAc/
hexane) 0.35; IR (neat, cmꢁ1) 3470, 3061, 3027, 2936, 2861, 2350
(w), 2210 (vw), 1723, 1601, 1451, 1316, 1283, 1250, 1107, 1071, 1024,
918, 754, 712; dH (400 MHz, CDCl3) 8.07e7.25 (10H, m), 6.71 (1H, s),
4.42 (1H, qrt, J¼6.2 Hz), 2.37e2.05 (4H, m), 1.78e1.40 (6H, m), 1.28
4.7.5. 2-Ethyl-2-methyl-6,7,8,8a-tetrahydro-2H-chromen-4-yl ben-
zoate 29 (two diastereomers). Yield 0.119 g (80%); Gummy liquid; Rf
(1% EtOAc/hexane) 0.30; IR (neat, cmꢁ1) 3063, 2970, 2939, 2867,
1739, 1599, 1449, 1257, 1087, 1020, 709; dH (400 MHz, CDCl3)
8.15e7.46 (10H, m), 5.72 and 5.71 (2H, two br s), 5.58 and 5.46 (2H,
two s), 4.48 and 4.43 (2H, two br s), 2.12e1.83 and 1.71e1.58 (16H,
m), 1.39 and 1.32 (6H, two s), 0.97 and 0.96 (6H, two t, J¼7.4 and
7.6 Hz, respectively) [two diastereomers were there and hence the
proton numbers are doubled in the assignment given here]; dC
(100.6 MHz, CDCl3) 164.7, 164.6, 142.7, 141.9, 133.5, 130.0, 129.9,

R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
8009
129.6, 129.5, 128.6, 122.7, 121.6, 121.2, 121.0, 75.1, 74.8, 67.5, 67.3,
35.5, 30.5, 29.24, 29.20, 25.9, 25.2, 24.2, 20.64, 20.61, 8.1; HRMS (ESI):
[MþþNa], found 321.1466. C19H22NaO3 requires 321.1467.
129.5, 128.6, 121.8, 120.9, 77.1, 67.4, 41.5, 39.9, 29.3, 25.3, 20.7, 17.1,
16.9, 14.8, 14.6; HRMS (ESI): [MþþNa], found 363.1933. C22H28NaO3
requires 363.1936.
4.7.6. 2,2-Dimethyl-6,7,8,8a-tetrahydro-2H-chromen-4-yl
acetate
4.7.12. 5-Benzyl-2H-Pyran-4-yl benzoate 36. Yield 0.094 g (64%);
Gummy liquid; Rf (1% EtOAc/hexane) 0.30; IR (neat, cmꢁ1) 3063,
3030, 2926, 1769, 1725, 1603, 1584, 1495, 1453, 1269, 1109, 1026,
938, 708; dH (400 MHz, CDCl3) 8.07e7.22 (11H, m), 6.35 (1H, s), 5.25
(2H, s), 3.76 (2H, s); dC (100.6 MHz, CDCl3) 166.3, 150.0, 140.3, 133.2,
129.9, 128.4, 126.4, 125.5, 112.4, 58.8, 31.3; HRMS (ESI): [MþþH],
found 293.1177. C19H17O3 requires 293.1179.
30. Yield 0.083 g (75%); Gummy liquid; Rf (1% EtOAc/hexane) 0.30;
IR (neat, cmꢁ1) 2976, 2940, 2870, 1759, 1680, 1634, 1435, 1372, 1198,
1144, 1084, 1040, 941, 901; dH (400 MHz, CDCl3) 5.65 (1H, t,
J¼3.6 Hz), 5.40 (1H, s), 4.39 (1H, br s), 2.19 (3H, s), 2.16e1.58 (6H,
m), 1.38 and 1.34 (6H, two s); dC (100.6 MHz, CDCl3) 168.8, 141.9,
129.7, 122.6, 121.1, 72.5, 67.6, 30.1, 29.2, 25.5, 25.3, 20.8, 20.7; HRMS
(ESI): [MþþH], found 223.1334. C13H19O3 requires 223.1336.
4.7.13. (Z)-3-Benzylidene-6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl
benzoate 37. Yield 0.144 g (90%); Gummy liquid; Rf (1% EtOAc/
hexane) 0.30; IR (neat, cmꢁ1) 3059, 2976, 2932, 2851, 1738, 1601,
1493, 1453, 1265, 1206, 1177, 1150, 1109, 1059, 1024, 704; dH
(400 MHz, CDCl3) 7.49e6.80 (10H, m), 6.41 (1H, s), 5.61 (1H, s), 4.48
(2H, d, J¼0.8 Hz), 1.46 (6H, s); dC (100.6 MHz, CDCl3) 164.2, 142.0,
136.5, 132.9, 129.7, 128.8, 128.6, 127.74, 127.70, 127.5, 126.8, 126.7,
125.8, 74.0, 66.7, 27.4; HRMS (ESI): [MþþNa], found 343.1310.
C21H20NaO3 requires 343.1310.
4.7.7. 6,7,8,8a-Tetrahydrospiro[chromene-2,10-cyclohexane]-4-yl ac-
etate 31. Yield 0.102 g (78%); Gummy liquid; Rf (1% EtOAc/hexane)
0.30; IR (neat, cmꢁ1) 2936, 2861, 1761, 1676, 1624, 1451, 1370, 1206,
1171, 1082, 737; dH (400 MHz, CDCl3) 5.63 (1H, br s), 5.48 (1H, s),
4.38 (1H, br s), 2.19 (3H, s), 2.15e2.14, 1.66e1.58 and 1.54e1.45
(16H, m); dC (100.6 MHz, CDCl3) 168.9, 142.3, 130.2, 122.0, 120.8,
73.4, 66.8, 38.4, 33.5, 29.3, 25.6, 25.3, 21.9, 21.7, 20.9, 20.7; HRMS
(ESI): [MþþNa], found 285.1465. C16H22NaO3 requires 285.1467.
4.7.8. 2,2-Dimethyl-6,7,8,8a-tetrahydro-2H-chromen-4-yl
pro-
4.7.14. (Z)-3-Benzylidene-1-oxaspiro[5.5]undec-4-en-4-yl benzoate
38. Yield 0.148 g (82%); Gummy liquid; [Found: C, 79.85; H, 6.76.
C24H24O3 requires C, 79.97; H, 6.71%]; Rf (1% EtOAc/hexane) 0.30; IR
(neat, cmꢁ1) 3059, 3027, 2932, 2857, 2245, 1960, 1738, 1601, 1493,
1449, 1262, 1186, 1069, 1024, 704; dH (400 MHz, CDCl3) 7.50e6.79
(10H, m), 6.40 (1H, s), 5.66 (1H, s), 4.46 (2H, s), 1.93e1.69 and
1.62e1.33 (10H, m); dC (100.6 MHz, CDCl3) 164.2, 142.3, 136.6, 132.9,
129.7, 128.9, 128.6, 127.9, 127.73, 127.70, 126.6, 126.4, 125.5, 74.8,
66.1, 35.5, 25.5, 21.7; LC/MS m/z 361 [Mþ1]þ.
pionate 32. Yield 0.086 g (73%); Gummy liquid; Rf (1% EtOAc/hex-
ane) 0.30; IR (neat, cmꢁ1) 2978, 2940, 2868, 1763, 1667, 1632, 1462,
1358,1177,1144,1080; dH (400 MHz, CDCl3) 5.64 (1H, br s), 5.40 (1H,
s), 4.40 (1H, br s), 2.50 (2H, qrt, J¼7.6 Hz), 2.16e1.86 and 1.60e1.58
(6H, m), 1.39 and 1.34 (6H, two s), 1.22 (3H, t, J¼7.6 Hz); dC
(100.6 MHz, CDCl3) 172.4, 141.7, 129.8, 122.5, 121.0, 72.5, 67.6, 30.1,
29.2, 27.5, 25.5, 25.3, 20.7, 9.2; HRMS (ESI): [MþþNa], found
259.1312. C14H20NaO3 requires 259.1310.
4.7.9. 2-Isobutyl-2-methyl-6,7,8,8a-tetrahydro-2H-chromen-4-yl
benzoate 33 (two diastereomers). Yield 0.127 g (78%); Gummy liq-
uid; Rf (1% EtOAc/hexane) 0.30; IR (neat, cmꢁ1) 3063, 3036, 2943,
2860,1743, 1660, 1633, 1600, 1458, 1386, 1370, 1255,1178, 1030, 915,
712; dH (400 MHz, CDCl3) 8.15e8.13 and 7.63e7.47 (10H, m), 5.71
(2H, s), 5.52 and 5.49 (2H, two s), 4.46 (2H, br s), 2.13e2.05,
1.91e1.80 and 1.69e1.45 (18H, m), 1.39 and 1.37 (6H, two s),
1.05e0.89 (12H, m) [two diastereomers were there and hence the
proton numbers are doubled in the assignment given here]; dC
(100.6 MHz, CDCl3) 164.7, 142.3, 141.9, 133.5, 130.1, 129.82, 129.80,
129.6,128.6, 123.4, 122.2, 121.0, 75.4, 75.2, 67.5, 67.3, 51.2, 45.6, 29.4,
29.1, 27.0, 25.5, 25.3, 25.2, 24.8, 24.5, 24.4, 24.3, 23.8, 20.7; HRMS
(ESI): [MþþNa], found 349.1778. C21H26NaO3 requires 349.1780.
4.7.15. (Z)-8-Benzylidene-6-oxaspiro[4.5]dec-9-en-9-yl
benzoate
39. Yield 0.149 g (86%); Gummy liquid; Rf (1% EtOAc/hexane) 0.30;
IR (neat, cmꢁ1) 3062, 3020, 2956, 2913, 2849, 1731, 1656, 1603,
1454, 1262, 1171, 1070, 804, 702; dH (400 MHz, CDCl3) 7.50e6.79
(10H, m), 6.40 (1H, s), 5.60 (1H, ws), 4.41 (2H, s), 2.06e2.01 (2H, m),
1.89 and 1.73 (6H, two br s); dC (100.6 MHz, CDCl3) 164.2, 142.1,
136.6, 132.9, 129.7, 128.9, 128.6, 127.7, 127.6, 126.6, 125.7, 125.6, 84.9,
67.4, 38.4, 24.2; HRMS (ESI): [MþþNa], found 371.1622. C23H24NaO3
requires 371.1623.
4.7.16. (Z)-3-Benzylidene-6-ethyl-6-methyl-3,6-dihydro-2H-pyran-
4-yl benzoate 40. Yield 0.107 g (64%); Gummy liquid; Rf (1% EtOAc/
hexane) 0.30; IR (neat, cmꢁ1): 2970, 2929, 2851, 1733, 1650, 1454,
1257, 1107, 1061, 1024; dH (400 MHz, CDCl3) 7.49e6.83 (10H, m),
6.41 (1H, s), 5.57 (1H, s), 4.54 and 4.38 (2H, 2 d, J¼12.4 Hz each),
1.78e1.73 (2H, m), 1.39 (3H, s), 1.03 (3H, t, J¼7.6 Hz); dC (100.6 MHz,
CDCl3) 164.3, 142.6, 136.6, 132.9, 129.7, 128.9, 128.6, 127.8, 127.7,
126.7, 125.9, 125.6, 76.4, 66.6, 33.7, 24.4, 8.2; HRMS (ESI): [MþþNa],
found 357.1467. C22H22NaO3 requires 357.1467.
4.7.10. 2-Methyl-2-pentyl-6,7,8,8a-tetrahydro-2H-chromen-4-yl
benzoate 34 (two diastereomers). Yield 0.128 g (82%); Gummy liq-
uid; Rf (1% EtOAc/hexane) 0.30; IR (neat, cmꢁ1) 2959, 2931, 2871,
1737, 1600, 1452, 1375, 1260, 1085, 1063, 1025, 701; dH (400 MHz,
CDCl3) 8.15e7.48 (10H, m), 5.72 (2H, br s), 5.57 and 5.48 (2H, two s),
4.48 (2H, br s), 2.18e2.07 and 1.87e1.26 (34H, m), 0.90 and 0.89
(6H, two t, J¼7.8 and 7.6 Hz, respectively) [two diastereomers were
there and hence the proton numbers are doubled in the assignment
given here]; dC (100.6 MHz, CDCl3) 164.7, 142.5, 141.9, 133.6, 130.1,
129.9, 129.7, 129.6, 128.6, 122.9, 122.0, 121.3, 121.1, 75.0, 74.8, 67.5,
67.4, 43.0, 37.9, 32.3, 29.3, 26.7, 25.3, 24.6, 23.5, 23.4, 22.7, 20.7, 14.3,
14.1; HRMS (ESI): [MþþNa], found 363.1938. C22H28NaO3 requires
363.1936.
4.7.17. (Z)-3-Benzylidene-6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl
acetate 41. Yield 0.096 g (74%); Gummy liquid; Rf (1% EtOAc/hex-
ane) 0.30; IR (neat, cmꢁ1) 3058, 3027, 2979, 2934, 1761, 1620, 1449,
1370, 1198, 1149, 1054, 1019, 900, 739, 700; dH (400 MHz, CDCl3)
7.30e7.22 (5H, m), 6.36 (1H, s), 5.45 (1H, s), 4.41 (2H, s), 1.40 (6H, s),
1.27 (3H, s); dC (100.6 MHz, CDCl3) 168.5, 141.9, 136.6, 129.2, 127.7,
127.2, 127.0, 126.7, 125.2, 73.8, 66.6, 27.3, 19.5; HRMS (ESI):
[MþþNa], found 281.1155. C16H18NaO3 requires 281.1154.
4.7.11. 2,2-Dipropyl-6,7,8,8a-tetrahydro-2H-chromen-4-yl benzoate
35. Yield 0.138 g (81%); Gummy liquid; Rf (1% EtOAc/hexane) 0.30;
IR (neat, cmꢁ1) 2959, 2940, 2866, 1737, 1458, 1277, 1173, 1085, 1025,
701; dH (400 MHz, CDCl3) 8.15e7.47 (5H, m), 5.69 (1H, br s), 5.50
(1H, s), 4.46 (1H, br s), 2.12e2.04 and 1.87e1.32 (14H, m), 0.96e0.87
(6H, m); dC (100.6 MHz, CDCl3) 164.8, 142.4, 133.5, 130.1, 129.9,
4.7.18. (Z)-3-Benzylidene-2-methyl-1-oxaspiro[5.5]undec-4-en-4-yl
benzoate 42. Yield 0.161 g (86%); Gummy liquid; [Found: C, 80.25;
H, 6.91. C25H26O3 requires C, 80.18; H, 7.00%]; Rf (1% EtOAc/hexane)
0.30; IR (neat, cmꢁ1): 3061, 2930, 2855, 1736, 1601, 1451, 1262, 1179,
1088, 1024, 739, 704; dH (400 MHz, CDCl3) 7.44e7.00 (10H, m), 6.46

8010
R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
(1H, s), 5.67 (1H, s), 4.61 (1H, qrt, J¼6.0 Hz),1.99e1.33 (10H, m), 1.53
(3H, br s); dC (100.6 MHz, CDCl3) 164.4, 143.0, 137.4, 133.1, 132.8,
130.2, 129.7, 129.0, 128.8, 127.7, 126.7, 125.9, 123.4, 74.2, 67.7, 38.6,
33.6, 25.6, 22.1, 21.7, 18.4; LC/MS m/z 377 [Mþ1]þ.
79.0 (2 d, J¼7.3 and 7.0 Hz, respectively), 75.2 (d, J¼14.1 Hz), 73.1 (d,
J¼166.2 Hz), 32.5 (d, J¼8.5 Hz), 29.5, 25.4, 22.4, 20.8; 31P NMR
(162 MHz, CDCl3)
d
9.0; HRMS (ESI): [MþþH], found 469.1782.
C26H30O6P requires 469.1782.
Compound 47. Yield 0.120 g (62%). The spectral data are in ac-
4.8. Synthesis of phosphorus containing b-hydroxy propargyl
cordance with the literature report.4e
esters 43e45
Compound 48. Yield 0.062 g (28%); Mp 96e98 ꢀC; Rf (40% EtOAc/
hexane) 0.25; IR (KBr, cmꢁ1) 3063, 3030, 2932, 2858, 1666, 1600,
1436, 1266, 1162, 1123, 707; dH (400 MHz, CDCl3) 8.10e7.47 and
7.25e7.16 (15H, m), 6.18 (1H, br s), 6.06 (1H, s), 4.12 (2H, s),
2.19e2.13 and 1.67e1.58 (8H, m); dC (100.6 MHz, CDCl3) 159.9 (d,
J¼6.2 Hz), 140.2, 140.0 (d, J¼6.3 Hz), 133.3, 132.8 (d, J¼100.7 Hz),
131.8, 131.7, 130.1, 129.0, 128.6, 128.4, 126.9, 126.1, 125.7, 107.1 (d,
J¼8.9 Hz), 31.2, 25.3, 24.8, 22.2, 22.0; 31P NMR (162 MHz, CDCl3)
Compound 43: This compound was synthesised by a literature
procedure18 by using 21 (0.300 g, 0.9 mmol), and H-phosphonate
(OCH2CMe2CH2O)P(O)H (0.131 g, 0.9 mmol). Yield 0.405 g (92%);
Mp 148e150 ꢀC; Rf (50% EtOAc/hexane) 0.40; IR (KBr, cmꢁ1) 3178,
2986, 2964, 2934, 2250 (vw), 1721, 1474, 1452, 1293, 1260, 1112,
1085, 833, 767, 712; dH (400 MHz, CDCl3) 8.04e7.27 (10H, m), 6.93
(d, J¼4.4 Hz), 4.79 (1H, dd, J¼11.2 and 5.4 Hz), 4.44e4.33 (2H, m),
4.05e3.90 (3H, m), 1.89 (6H, s), 1.18 and 0.88 (6H, two s); dC
(100.6 MHz, CDCl3) 165.6, 137.8 (d, J¼11.1 Hz), 135.3 (d, J¼2.1 Hz),
133.3, 130.5, 129.7, 129.1, 128.9, 128.4, 128.2, 116.3, 99.5, 81.2 (d,
J¼4.2 Hz), 78.14, 78.10, 73.7 (d, J¼159.0 Hz), 73.1, 32.5 (d, J¼7.6 Hz),
28.7, 28.6, 22.0, 20.8; 31P NMR (162 MHz, CDCl3) 12.9; HRMS (ESI):
[MþþH], found 469.1781. C26H30O6P requires 491.1781.
d
18.5; HRMS (ESI): [MþþH], found 439.1828. C29H28O2P requires
439.1828.
4.10. Synthesis of b-hydroxy propargylic esters 49, 50
These compounds were synthesised by following a procedure
similar to that for 15e20.
Compound 44: This compound was synthesised by using 22
(0.300 g, 0.8 mmol), and H-phosphonate (OCH2CMe2CH2O)P(O)H
(0.131 g, 0.9 mmol). Yield 0.387 g (91%); Mp 190e192 ꢀC; Rf (50%
EtOAc/hexane) 0.40; IR (neat, cmꢁ1) 3150, 2970, 2931, 2855, 2300
(vw), 1720, 1447, 1282, 1255, 1195, 1112, 1085, 1052, 1019, 833, 811,
762, 707; dH (400 MHz, CDCl3) 8.05e7.29 (10H, m), 6.92 (1H, d,
J¼4.0 Hz), 4.78 (1H, d, J¼10.8 Hz), 4.45e4.41 and 4.33e4.28 (2H, m),
4.05e3.89 (2H, m), 2.37e2.05 and 1.81e1.75 (10H, m), 1.18 and 0.87
(6H, two s); dC (100.6 MHz, CDCl3) 165.6, 137.7, 137.6, 135.4, 133.3,
130.7, 129.7, 129.1, 128.8, 128.5, 128.2, 116.5, 98.9, 83.9 (d, J¼3.4 Hz),
78.1 (dd/t, J¼6.8 Hz each), 73.9 (d, J¼157.9 Hz), 36.9, 36.8, 32.5 (d,
J¼7.2 Hz), 25.1, 22.6, 22.5, 22.0, 20.8; 31P NMR (162 MHz, CDCl3)
12.9; HRMS (ESI): [MþþNa], found 531.1913. C29H33NaO6P requires
531.1913.
Compound 45: This compound was synthesised by using 22
(0.300 g, 0.8 mmol), and phosphine oxide Ph2P(O)H (0.162 g,
0.8 mmol). Yield 0.400 g (85%); Gummy liquid; [Found: C, 77.32; H,
5.85. C36H33O4P requires C, 77.13; H, 5.93%]; Rf (50% EtOAc/hexane)
0.35; IR (neat, cmꢁ1) 3448, 3059, 2935, 2858, 2200 (vw), 1719, 1600,
1437, 1282, 1245, 1107, 713; dH (400 MHz, CDCl3) 8.02e7.28 (20H,
m), 6.90 (1H, d, J¼4.0 Hz), 5.19 (1H, d, J¼6.0 Hz),1.95e1.36 (10H, m);
dC (100.6 MHz, CDCl3) 165.0, 137.7, 137.6, 135.6, 133.1, 132.6, 132.5,
132.2, 132.1, 131.9, 131.5, 130.9, 129.7, 129.0, 128.6, 128.32, 128.30,
128.2, 128.1, 116.4, 99.1, 83.0, 75.9 (d, J¼79.5 Hz), 74.7, 36.7, 36.5,
25.0, 22.4; 31P NMR (162 MHz, CDCl3) 28.9; LC/MS m/z 561 [Mþ1]þ.
4.10.1. (E)-1-(3-(Hydroxymethyl)-4-phenylbut-3-en-1-ynyl)cyclo-
hexyl acetate 49. This compound was synthesised from 2 (400 mg,
1.54 mmol) and 3g (1.5 equiv). Yield 0.268 g (56%); Gummy liquid;
[Found: C, 76.58; H, 7.36. C19H22O3 requires C, 76.48; H, 7.43%]; Rf
(20% EtOAc/hexane) 0.35; IR (neat, cmꢁ1) 3461, 3060, 3025, 2938,
2861, 2310 (w), 2190 (vw), 1742, 1601, 1495, 1449, 1368, 1267, 1233,
1022, 963, 916, 756, 694; dH (400 MHz, CDCl3) 7.84e6.71 (6H, m),
4.28 (2H, d, J¼4.8 Hz), 2.60 (1H, br s), 2.24e2.21 (2H, m), 2.07 (3H,
s), 1.90e1.57 (8H, m); dC (100.6 MHz, CDCl3) 169.9, 135.9, 133.7,
128.7, 128.3, 128.2, 121.5, 97.8, 84.1, 76.1, 67.4, 37.0, 25.2, 22.7, 22.1;
LC/MS m/z 299 [Mþ1]þ.
4.10.2. (E)-5-(Hydroxymethyl)-2-methyl-6-phenylhex-5-en-3-yn-2-
yl propionate 50. This compound was synthesised from 2 (400 mg,
1.54 mmol) and 3h (1.5 equiv). Yield 0.327 g (78%); Gummy liquid;
Rf (20% EtOAc/hexane) 0.35; IR (neat, cmꢁ1) 3459, 3059, 2986, 2940,
2867, 2350 (vw), 2210 (w), 1742, 1599, 1449, 1381, 1362, 1254, 1190,
1125, 1078, 918, 874, 808, 756, 694; dH (400 MHz, CDCl3) 7.83e6.72
(6H, m), 4.27 (2H, s), 2.52 (1H, br s), 2.33 (3H, qrt, J¼6.8 Hz), 1.74
(6H, s), 1.14 (3H, t, J¼7.4 Hz); dC (100.6 MHz, CDCl3) 173.3, 135.8,
133.8, 128.6, 128.2, 128.1, 121.1, 98.2, 82.1, 72.2, 66.9, 28.8, 28.3, 9.0;
HRMS (ESI): [MþþNa], found 295.1310. C17H20NaO3 requires
295.1310.
4.9. General procedure for the synthesis of phosphono-/
4.11. Synthesis of macrocycles 51a,b and 52
phosphinoyl-furans and pyran derivatives 46e48
These compounds were synthesised by following a procedure
similar to that for 25e42 by using one of the hydroxy propargylic
esters (49e50, 0.5 mmol).
To a solution of one of the hydroxy propargylic esters 43e45
(0.5 mmol) in dry DCM (1 mL) was added a solution of Ph3PAuCl
(0.03 mol equiv) and AgSbF6 (0.03 mol equiv) in DCM (1.0 mL). The
contents were stirred at 70 ꢀC (oil bath temperature) till the starting
material was consumed. The solvent was removed under vacuum
and crude product was purified by column chromatography using
silica gel with ethyl acetate/hexane (1:1) mixture as eluent to afford
one of the products 46e48.
Compound 51a. Yield 0.033 g (28%); White solid; Mp 12
0e122 ꢀC; [Found: C, 85.56; H, 7.71. C34H36O2 requires C, 85.67; H,
7.61%]; Rf (1% EtOAc/hexane) 0.33; IR (KBr, cmꢁ1) 3058, 3025, 2934,
2857, 1721, 1599, 1449, 1339, 1289, 1260, 1144, 1084, 752, 693; dH
(400 MHz, CDCl3) 7.85e7.23 (10H, m), 6.88 (2H, s), 4.34 (4H, s),
2.06e1.55 and 1.35e1.29 (20H, m); dC (100.6 MHz, CDCl3) 136.5,
132.9, 128.7, 128.1, 127.9, 119.6, 97.3, 84.6, 75.2, 66.9, 37.3, 25.6, 23.0;
LC/MS m/z 475 [Mꢁ1]þ.
Compound 46. Yield 0.103 g (44%); Mp 134e138 ꢀC; Rf (40%
EtOAc/hexane) 0.25; IR (KBr, cmꢁ1) 3058, 2964, 2926, 2855, 1737,
1658, 1452, 1249, 1195, 1096, 1069, 1014, 811, 723; dH (400 MHz,
CDCl3) 8.12e6.88 (11H, m), 5.75 (1H, d, J¼0.8 Hz), 5.19 (1H, dd,
J¼13.0 and 1.4 Hz), 4.60 (2H, dd, J¼18.8 and 10.0 Hz), 4.09e3.94
(2H, m), 1.52 and 1.49 (6H, two s), 1.35 and 0.90 (6H, two s); dC
(100.6 MHz, CDCl3) 164.0, 142.2 (d, J¼12.9 Hz), 136.7, 133.4, 133.0,
130.1, 129.6, 128.8, 128.7, 128.4, 127.7, 126.9, 125.6, 123.4, 79.9 and
Compound 51b. Yield 0.052 g (44%); White solid; Mp 17
8e180 ꢀC; Rf (1% EtOAc/hexane) 0.30; IR (KBr, cmꢁ1) 2963, 2856,
1948,1599,1495,1447,1412,1262,1103, 866, 801, 693; dH (400 MHz,
CDCl3) 7.91e7.27 (10H, m), 6.71 (2H, s), 4.38 (4H, s), 2.12e1.63 (18H,
m), 1.32 (2H, br s); dC (100.6 MHz, CDCl3) 136.0, 128.8, 128.4, 128.1,
119.9, 98.9, 84.8, 76.8, 70.3, 37.5, 25.6, 23.3; HRMS (ESI): [MþþH],

R. Kotikalapudi, K.C. Kumara Swamy / Tetrahedron 69 (2013) 8002e8012
8011
8195; (d) Chen, Y.; Liu, Y. J. Org. Chem. 2011, 76, 5274 (carbocycles); (e) Koti-
kalapudi, R.; Kumara Swamy, K. C. Tetrahedron Lett. 2012, 53, 3831.
5. Zhang, D.; Yuan, C. Eur. J. Org. Chem. 2007, 3916.
found 477.2793. C34H37O2 requires 477.2795. X-ray structure has
been determined for this compound.
Compound 52. Yield 0.059 g (60%); Low melting solid; Rf (1%
EtOAc/hexane) 0.30; IR (KBr, cmꢁ1) 2978, 2932, 2859, 2170, 2160,
1659, 1622, 1449, 1360, 1179, 1150, 1073, 739, 696; dH (400 MHz,
CDCl3) 7.84e7.29 (10H, m), 6.67 (2H, s), 4.37 (4H, s), 1.61 (12H, s); dC
(100.6 MHz, CDCl3) 136.0,135.8,128.6,128.5,128.2,119.5, 99.6, 83.0,
72.7, 71.0, 28.9; HRMS (ESI): [MþþNa], found 419.1989. C28H28NaO2
requires 419.1987.
6. (a) Chatgilialoglu, C.; Griller, D.; Lesage, M. J. Org. Chem. 1988, 53, 3642; (b)
Tanaka, J. I.; Higa, T. Tetrahedron Lett. 1996, 37, 5535; (c) Berberich, S. M.;
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Schneider, M. F.; Martin, S. F. Tetrahedron 2003, 59, 6819; (d) Ishibashi, M.;
Moor, R. E.; Patterson, G. M. L.; Xu, C.; Clardy, J. J. Org. Chem. 1986, 51, 5300; (e)
Hayakawa, H.; Miyashita, M. Tetrahedron Lett. 2000, 41, 707; (f) Faulkner, D. J.
Nat. Prod. Rep. 2000, 17, 7; (g) Kusumi, T.; Igari, M.; Ishitsuka, M. O.; Ichikawa,
A.; Itezono, Y.; Nakayama, N.; Kakisawa, H. J. Org. Chem. 1990, 55, 6286; (h)
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Kuzenetsov, G.; Johannes, C. W.; Tremblay, M. R.; Zhao, H.; Pesant, M.; Fang, F.
G.; Vermeulen, M. W.; Gallagher, B. M., Jr.; Littlefield, B. A. Anticancer Res. 2007,
27, 1509.
Single crystal X-ray data for compounds 27 and 51b were col-
lected on a Bruker AXS-SMART or OXFORD diffractometer using Mo
ꢀ
Ka
(l
¼0.71073 A) radiation. The structures were solved by direct
methods and refined by full-matrix least squares method using
standard procedures.26 Absorption corrections were done using
SADABS program, where applicable. In general, all non-hydrogen
atoms were refined anisotropically; hydrogen atoms were fixed
by geometry or located by a Difference Fourier map and refined
isotropically.
8. (a) Ichihara, A.; Oikawa, H. Curr. Org. Chem. 1998, 2, 365; (b) Tietze, L. F.;
€
Bohnke, N.; Dietz, S. Org. Lett. 2009, 11, 2948; (c) Hayman, C. M.; Larsen, D. S.;
Simpson, J.; Bailey, K. B.; Gill, G. S. Org. Biomol. Chem. 2006, 4, 2794; (d) Audrain,
H.; Thorauge, J.; Hazell, R. G.; Jørgensen, K. A. J. Org. Chem. 2000, 65, 4487; (e)
Tietze, L. F.; Montenbruck, A.; Schneider, C. Synlett 1994, 509; (f) Tietze, L. F.;
Schneider, C.; Montenbruck, A. Angew. Chem., Int. Ed. Engl. 1994, 33, 980; (g)
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Tietze, L. F.; Hartfiel, U.; Hubsch, T.; Voss, E.; Bogdanowiczszwed, K.; Wich-
mann, J. Liebigs Ann. Chem. 1991, 275; (h) De Gaudenzi, L.; Apparao, S.; Schmidt,
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Bennabi, S.; Narkunan, K.; Rousset, L.; Bouchu, D.; Ciufolini, M. A. Tetrahedron
Lett. 2000, 41, 8873.
Compound 27: colourless block, C21H24O3, M¼320.40, Ortho-
rhombic, Space group Pn21a3
,
a¼10.0016(6), b¼9.3235(8),
ꢀ
ꢀ
c¼18.6290(17) A, V¼1737.2(2) A , Z¼4,
m
¼0.082 mmꢁ1, data/re-
straints/parameters: 2763/1/217, Flack parameter ꢁ1.4(15), R in-
10. Perrett, S.; Whitfield, P. J. Phytother. Res. 1995, 9, 401.
dices (I>2
s
(I)): R1¼0.0557, wR2 (all data)¼0.0934. The
11. De Brabander, J. K.; Liu, B.; Qian, M. Org. Lett. 2008, 12, 2533.
12. Selected references in the formation of 5-membered heterocycles via gold
catalysis: (a) Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804; (b) Suhre, M. H.;
Reif, M.; Kirsch, S. F. Org. Lett. 2005, 7, 2005; (c) Buzas, A.; Istrate, F.; Gagosz,
F. Org. Lett. 2006, 8, 1957; (d) Morita, N.; Krause, N. Angew. Chem., Int. Ed.
2006, 45, 1897; (e) Schwier, T.; Sromek, A. W.; Yap, D. M. L.; Chernyak, D.;
Gevorgyan, V. J. Am. Chem. Soc. 2007, 129, 9868; (f) Zhang, Z.; Bender, C. F.;
Widenhoefer, R. A. J. Am. Chem. Soc. 2007, 129, 14148; (g) Winter, C.; Krause,
N. Green Chem. 2009, 11, 1309; (h) Egi, M.; Azechi, K.; Saneto, M.; Shimizu,
K.; Akai, S. J. Org. Chem. 2010, 75, 2123; (i) Krause, N.; Winter, C. Chem. Rev.
2011, 111, 1994; (j) Alcaide, B.; Almendros, P.; Alonso, J. M. Org. Biomol. Chem.
2011, 9, 4405.
configuration at C1 as shown by checkcif is R. CCDC No. 924016.
Compound 51b: colourless block, C34H36O2, M¼476.63, Mono-
ꢀ
clinic, Space group C2/c, a¼28.650(4), b¼9.830(1), c¼22.383(2) A,
3
ꢀ
b
¼121.74(2), V¼5361(1) A , Z¼8,
m
¼0.071 mmꢁ1, data/restraints/
parameters: 4715/0/325, R indices (I>2
data)¼0.1180, CCDC No. 924018.
s(I)): R1¼0.1562, wR2 (all
Acknowledgements
13. (a) Sherry, B. D.; Maus, L.; Laforteza, B. N.; Toste, F. D. J. Am. Chem. Soc. 2006, 128,
8132; (b) Gockel, B.; Krause, N. Org. Lett. 2006, 8, 4485; (c) Lalonde, R. L.; Sherry,
B. D.; Kang, E. J.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2452; (d) Piera, J.;
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14. Wang, Y. M.; Kuzniewski, C. N.; Rauniyar, V.; Hoong, C.; Toste, F. D. J. Am. Chem.
Soc. 2011, 133, 12972.
We thank Department of Science & Technology (DST, New Delhi)
for financial support, single crystal X-ray diffractometer and HRMS
facility. K.C.K. thanks DST for a J.C. Bose fellowship. R.K. thanks CSIR
(New Delhi) for a fellowship.
€
15. (a) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585; (b) Farina, V. Pure &
Appl. Chem. 1996, 68, 73.
Supplementary data
16. Lautens, M.; Maddess, M. L.; Sauer, E. L. O.; Quellet, S. G. Org. Lett. 2002, 4, 83.
17. (a) Chakravarty, M.; Kumara Swamy, K. C. J. Org. Chem. 2006, 71, 9128; (b)
Bhuvan Kumar, N. N.; Nagarjuna Reddy, M.; Kumara Swamy, K. C. J. Org. Chem.
2009, 74, 5395; (c) Srinivas, V.; Sajna, K. V.; Kumara Swamy, K. C. Tetrahedron
Lett. 2011, 52, 5323.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.07.003.
18. Muthiah, C.; Praveen Kumar, K.; Aruna Mani, C.; Kumara Swamy, K. C. J. Org.
Chem. 2000, 65, 3733.
References and notes
19. Phosphono-alkynols 53, 54 led to phosphono-furans 55, 56, respectively, in
addition to the corresponding phosphono-pyrans 550, 560. In these cases, two
products, a phosphonofuran and a phosphonopyran with very close Rf values
were formed in varying proportions [31P NMR evidence], but the reaction was
quantitative and the phosphono-alkynol completely consumed. We could iso-
late the phosphono-furans 55, 56 (see Supplementary data; and CCDC 924017
for 56) in a pure state.
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O
OH
P
R
R
OBz
3 mol % Ph3PAuCl/ AgSbF6
DCE, 70 oC, 3 h
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53-54
(CH2)n
O
R
O
R
P
R
P
R
O
Ph
BzO
O
+
(CH2)n
Ph
(CH2)n
55', 55 % (purity~80 %)
56', 10 % (purity~95 %)
R = O-i-Pr, n = 3
(55, 33 %)
€
K.; Haffner, T.; Rudolph, M.; Rominger, F. Eur. J. Org. Chem. 2011, 667; (c)
(RR) = OCH2CMe2CH2O, n = 2 (56, 64 %, X-ray)
Hashmi, A. S. K.; Haffner, T.; Rudolph, M.; Rominger, F. Chem.dEur. J. 2011, 17,

8012
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